title: The association between silica exposure and development of ANCA-associated vasculitis: systematic review and meta-analysis.
abstract: BACKGROUND
  Crystalline silica is among the environmental exposures associated with increased risk of autoimmune diseases, including rheumatoid arthritis, systemic sclerosis and systemic lupus erythematosus. Silica exposure has also been related to the development of ANCA-associated vasculitides (AAV), but past studies appear to conflict as to the presence and magnitude of the associated risks of disease. We aimed to conduct a systematic review of the existing studies and meta-analysis of their results.
  
  
  METHODS
  We searched EMBASE, MEDLINE and international scientific conference abstract databases for studies examining the association of silica exposure with AAV. Studies in English, French, or Spanish were included and those examining the association of silica with ANCA-positivity alone were excluded. We assessed study quality using the Newcastle-Ottawa Scale. We meta-analyzed the results using random effects models and tested for heterogeneity. We performed sensitivity and subgroup analyses, examining studies that adjusted for smoking and occupational risk factors as well as studies that analyzed by subtypes of AAV.
  
  
  RESULTS
  We identified 158 potential manuscripts and 3 abstracts related to silica exposure and risk of AAV. 147 were excluded after abstract review and 14 underwent detailed evaluation of full manuscript/abstract. After further application of exclusion criteria, 6 studies (all cases-controls) remained. The studies had moderate heterogeneity in selection of cases and controls, exposure assessment, disease definition and controlling for potential confounders. We found an overall significant summary effect estimate of silica "ever exposure" with development of AAV (summary OR 2.56, 95% CI 1.51-4.36), with moderate heterogeneity (I(2)=48.40%). ORs were similar for studies examining only MPA (OR 3.95, CI 95% 1.89-8.24), compared to those only studying GPA (OR 3.56, CI 95% 1.85-6.82).
  
  
  CONCLUSIONS
  Despite moderate heterogeneity among studies, the totality of the evidence after meta-analysis points to an association between silica exposure and risk for developing AAV.
authors.affiliation: Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Boston, MA, United States. Electronic address: JGOMEZPUERTA@PARTNERS.ORG.
authors.forename: José A
authors.initials: JA
authors.lastname: Gómez-Puerta
authors.forename: Lydia
authors.initials: L
authors.lastname: Gedmintas
authors.forename: Karen H
authors.initials: KH
authors.lastname: Costenbader
mesh_terms: D056648:Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis / Q000139:chemically induced*; D019268:Antibodies, Antineutrophil Cytoplasmic / Q000276:immunology; D004781:Environmental Exposure; D006801:Humans; D012307:Risk Factors; D012822:Silicon Dioxide / Q000633:toxicity*
chemical_list: D019268:Antibodies, Antineutrophil Cytoplasmic; D012822:Silicon Dioxide
keywords: ANCA-associated vasculitides; Antineutrophil cytoplasmic antibodies; Meta-analysis; Silica